Genetic Variant PLEKHA1:p.Arg233Arg (chr10-122424216-T-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP7

The NM_001001974.4(PLEKHA1):c.699T>A(p.Arg233Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PLEKHA1
NM_001001974.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.57

Publications

31 publications found

Variant links:

Genes affected

PLEKHA1 (HGNC:14335): (pleckstrin homology domain containing A1) This gene encodes a pleckstrin homology domain-containing adapter protein. The encoded protein is localized to the plasma membrane where it specifically binds phosphatidylinositol 3,4-bisphosphate. This protein may be involved in the formation of signaling complexes in the plasma membrane. Polymorphisms in this gene are associated with age-related macular degeneration. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 5.[provided by RefSeq, Sep 2010]

PLEKHA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP7

Synonymous conserved (PhyloP=-1.57 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001974.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLEKHA1	NM_001001974.4	MANE Select	c.699T>A	p.Arg233Arg	synonymous	Exon 9 of 12	NP_001001974.1
PLEKHA1	NM_001377230.1		c.699T>A	p.Arg233Arg	synonymous	Exon 10 of 13	NP_001364159.1
PLEKHA1	NM_001377231.1		c.699T>A	p.Arg233Arg	synonymous	Exon 12 of 15	NP_001364160.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PLEKHA1	ENST00000368990.8	TSL:1 MANE Select	c.699T>A	p.Arg233Arg	synonymous	Exon 9 of 12	ENSP00000357986.3
PLEKHA1	ENST00000392799.7	TSL:1	c.699T>A	p.Arg233Arg	synonymous	Exon 10 of 13	ENSP00000376547.3
PLEKHA1	ENST00000433307.2	TSL:1	c.699T>A	p.Arg233Arg	synonymous	Exon 8 of 11	ENSP00000394416.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

143846

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

221372

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1432446

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

712326

African (AFR)

AF:

0.00

AC:

AN:

31244

American (AMR)

AF:

0.00

AC:

AN:

36006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25280

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

79770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52830

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5052

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103780

Other (OTH)

AF:

0.00

AC:

AN:

59048

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

143846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69274

African (AFR)

AF:

0.00

AC:

AN:

38884

American (AMR)

AF:

0.00

AC:

AN:

14134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

4956

South Asian (SAS)

AF:

0.00

AC:

AN:

4438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66628

Other (OTH)

AF:

0.00

AC:

AN:

1962

Alfa

AF:

0.00

Hom.:

105616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.35

(source)

DANN

Benign

0.53

PhyloP100

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over